It Is the central tenant of Core B and this program project that the most appropriate method to study MH is in murine models that express frequently observed human MH mutations and in genotyped human tissue. Mouse models provide sufficient tissues for molecular, biochemical, cellular, physiological and morphologic analyses by a multidisciplinary team whose collective goal is to understand this myopathy. Genotyped human myotubes will allow direct correlation of the observed phenotypes between humans and mice with the same mutations and fixed and frozen human tissues will allow morphologic and biochemical comparisons. Core B will perform repetitive tasks that are necessary to support all three Projects and Core D. This core will produce and genotype the 4 existing MH knock-in mice, 2 transgenic mice, and breed, genotype and maintain MH mice crossed with dnTrp6 and SERCA1 overexpression transgenic mice. It will also assure that the long-term pharmacological interventions with salicylamine and 4-OH-BDE49 are carried out. It will distribute these mice or frozen muscles for study by all three Projects as needed and provide fixed muscles from these mice at different ages and genders to Core D. Core B will make myoblast cell lines from all heterozygous and homozygous MH knock-in mice, to be used by all 3 projects. If needed homozygous myoblasts will be obtained from El8 embryos from timed matings in cases where there is homozygous lethality as was the case for the R163C and Y522S RyRI mice. Core B will receive, expand and maintain genotyped human MHS myoblasts from Core C and distribute these to the projects. It will also distribute genotyped glutaraldehyde fixed human biopsy samples to Core D and frozen muscle samples to Project 2 received from Core C. Core B has and will receive new MHS mutations from Core C Discovery, prepare mutated cDNA constructs in mammalian expression vectors for project 3, and where possible lentiviral vectors and permanently transduced cells and where not ,HSV vectors to be distributed to projects 1 and 2 for their analyses. The uniform and consistent supply of exactly the same study models to all three Projects and Core D by this Core will allow a truly integrated approach to the study of malignant hyperthermia.